RESUMEN
BACKGROUND: In light of the poor prognosis for cervical cancer, research continues into the development of innovative and efficacious treatment modalities for this disease. We investigated the role of hepatocyte growth factor activator inhibitor-2 (HAI-2) and evaluated its clinical importance in cervical cancer. PATIENTS AND METHODS: HAI-2 expression was examined in cervical cancer specimens (n=52) by immunohistochemistry. We further attempted to investigate the biological functions and inhibitory effects of HAI-2 using human papillomavirus (HPV) 16 type SiHa and HPV 18 type HeLa cervical cancer cell lines. RESULTS: There were significant correlations between HAI-2 expression and stage (P=0.017), lymph node metastasis (P=0.005) and ovarian metastasis (P=0.038). Low HAI-2 expression was a significant predictor for a poor prognosis compared with high HAI-2 expression (disease-free survival rate, P=0.016; overall survival rate, P=0.021). After transient transfection into the SiHa and HeLa cell lines, HAI-2 showed potential inhibitory effects mediated by reductions in hepsin and matriptase expression, which led to apoptosis by increasing the level of Bak and reducing the level of Bcl-2. CONCLUSIONS: The present findings indicate that low HAI-2 expression in cervical cancer may be associated with a poor prognosis. We propose that HAI-2 may represent a therapeutic target for the treatment of cervical cancer.
Asunto(s)
Apoptosis , Biomarcadores de Tumor , Carcinoma de Células Escamosas/diagnóstico , Glicoproteínas de Membrana/fisiología , Neoplasias del Cuello Uterino/diagnóstico , Adenocarcinoma/diagnóstico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adulto , Anciano , Apoptosis/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/fisiología , Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/genética , Carcinoma Adenoescamoso/metabolismo , Carcinoma Adenoescamoso/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Proliferación Celular , Femenino , Células HeLa , Humanos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Pronóstico , Transducción de Señal/genética , Transfección , Células Tumorales Cultivadas , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/patologíaRESUMEN
We had previously reported that REIC/Dkk-3, a member of the Dickkopf (Dkk) gene family, works as a tumor suppressor. In this study, we evaluated the therapeutic effects of an intratumoral injection with adenoviral vector encoding REIC/Dkk-3 gene (Ad-REIC) using an orthotopic mouse prostate cancer model of RM-9 cells. We also investigated the in vivo anti-metastatic effect and in vitro anti-invasion effect of Ad-REIC gene delivery. We demonstrated that the Ad-REIC treatment inhibited prostate cancer growth and lymph node metastasis, and prolonged mice survival in the model. These therapeutic responses were consistent with the intratumoral apoptosis induction and in vitro suppression of cell invasion/migration with reduced matrix metalloprotease-2 activity. We thus concluded that in situ Ad-REIC/Dkk-3 gene transfer may be a promising therapeutic intervention modality for the treatment of prostate cancer.
Asunto(s)
Adenoviridae/genética , División Celular/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Modelos Biológicos , Metástasis de la Neoplasia/genética , Neoplasias de la Próstata/patología , Transfección , Proteínas Adaptadoras Transductoras de Señales , Animales , Apoptosis , Línea Celular Tumoral , Quimiocinas , Inyecciones Intralesiones , Masculino , Ratones , Ratones Endogámicos C57BL , Neoplasias de la Próstata/genéticaRESUMEN
Human endothelial dysfunction is a common feature in many diseases of pregnancy, such as gestational diabetes (GD). Metabolic changes include abnormal synthesis of nitric oxide (NO) and abnormal membrane transport of l-arginine and adenosine in primary cultures of human umbilical vein (HUVEC, macrovascular) and placental microvillus (hPMEC, microvascular) endothelial cells. These alterations are associated with modifications in the expression and activity of endothelial (eNOS) and inducible (iNOS) NO synthases, respectively, an effect that is maintained at least up to passage 5 in culture. HUVEC and hPMEC exhibit expression and activity of the human cationic amino acid transporter 1 (hCAT-1), equilibrative nucleoside transporters 1 (hENT1) and hENT2, as well as the corresponding SLC7A1, SLC29A1 and SLC29A2 gene promoter activities. Altered gene expression results from increased NO level, protein kinase C, mitogen-activated protein kinases, and hCHOP-C/EBPα transcription factor activation. Reduced ENT-mediated adenosine transport in GD is associated with stimulation of the l-arginine/NO pathway, and mainly due to reduced expression and activity of hENT1. In addition, hENT2 activity seems able to restore the reduced adenosine transport in GD. Additionally, insulin exerts a differential modulation of endothelial cells from macrocirculation compared with microcirculation, possibly due to expression of different insulin receptor isoforms. It is suggested that a common functional characteristic leading to changes in the bioavailability of adenosine and metabolism of l-arginine is evidenced by human fetal micro and macrovascular endothelium in GD.
Asunto(s)
Diabetes Gestacional/fisiopatología , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Microvasos/fisiopatología , Placenta/irrigación sanguínea , Placenta/fisiopatología , Diabetes Gestacional/metabolismo , Endotelio Vascular/citología , Femenino , Humanos , Microvasos/citología , Microvasos/metabolismo , Placenta/citología , Placenta/metabolismo , EmbarazoRESUMEN
Niños con infecciones a repetición es tal vez uno de los motivos más frecuentes de interconsulta al inmunólogo. En caso de pacientes pediátricos, los padres cuando nos traen al niño por primera vez, generalmente presentan un gran nivel de ansiedad. La exacta frecuencia de las inmunodeficiencias primarias en la población en general no es conocida, pero la estimación de la mayoría de los autores es que ésta es baja, si se excluye la deficiencia selectiva de la inmunoglobulina A. A pesar de ésto, cuando se presenta un enfermo con la historia clínica de infecciones a repetición, frecuentemente el médico tiene la tendencia a pensar primero en la posibilidad de algún problema primario del sistema inmunitario. Por la importancia y extensión del tema, se publicará en dos partes. En el presente número de Pediatría al Día, se abordarán los aspectos clínicos. En el próximo número se analizarán los aspectos de laboratorio
Asunto(s)
Lactante , Preescolar , Niño , Humanos , Síndromes de InmunodeficienciaRESUMEN
Los exámenes de laboratorio necesarios para el estudio de estos enfermos se pueden dividir en aquellos destinados a buscar el agente etiológico de las infecciones a repetición, y aquellos destinados a confirmar o descartar la sospecha clínica de una inmunodeficiencia primaria. Estos últimos a su vez se pueden dividir en exámenes inmunológicos iniciales o de descarte y aquellos exámenes más avanzados que sirven para caracterizar apropiadamente el defecto que se esta sospechando o para detectar anomalías inmunológicas más sutiles